1. Field of the Invention
The present invention involves two processes for the transformation of a .DELTA..sup.16 -steroid to a .DELTA..sup.17(20) -20-silyl ether which is a useful intermediate in the synthesis of corticoids.
2. Description of the Related Art
A copper iodide catalyzed conjugate reduction of an .alpha.,.beta.-unsaturated ketone (cyclohex-2-enone) by lithium aluminum hydride (LAH) in hexamethylphosphoric triamide (HMPA)/THF is reported in J. Chem. Soc. Chem. Comm., 1013 (1980). Similarly, J. Org. Chem., 51, 537 (1986) reports conjugate reduction of a steroidal .alpha.,.beta.-unsaturated ketone (progesterone) with diisobutylaluminum hydride (DIBAH), catalytic amount of methylcopper(I) and HMPA to give 84% of the reduced A-ring and 6% of the corresponding 20-hydroxy-.DELTA..sup.4 -3-ketone When this process was applied to the .DELTA..sup.16 -steroids (I) of the present invention, the steroid A-ring was not reduced, but there was selective reduction of the .DELTA..sup.16 -20-keto functionality at the D-ring. The conjugate reduction process of the present invention is operable with both .DELTA.4-3-keto and .DELTA..sup.1,4 -3-keto steroids
Syn. Comm. 16, 639 (1986) and J. Org. Chem., 52 439 (1987) both report the reaction of an .alpha.,.beta.-unsaturated ketone with DIBAH, a catalytic amount of methylcopper(I) and HMPA. The latter reference reports when the aluminum enolate produced was silylated the product produced was the reduced silyl enol ether, stating "The high efficiency of the conjugate reduction indicates the quantitative formation of the aluminum enolate by the hydroalumination of .alpha.,.beta.-unsaturated carbonyl compounds with DIBAH-HMPA." When this process was performed on the .DELTA..sup.16 -steroids (I) of the present invention, no evidence of any silyl enol ether was observed.
Tet. Lett. 26, 6015 (1985), ibid 26, 6019 (1985), ibid 27, 4025 (1986) and ibid 27, 4029 (1986) all describe the reaction of conjugated carbonyl compounds with organocopper reagents in the presence of trimethylsilyl chloride to give the expected silyl enol ether. The silylating agent not only accelerated the reactions but also gave higher yields. When the copper catalyzed conjugate reduction of the .DELTA..sup.16 -steroids (I) of the present invention was performed in the presence of trimethylsilyl chloride only a small amount of the silyl enol ether (III) was formed.
U.S. Pat. No. 4,568,492 discloses the reaction of .DELTA..sup.16 -steroids with trimethylsilyl chloride catalyzed by (.phi.P).sub.3 RhCl to give the .DELTA..sup.17(20) -20-silyl enol ether, but we have found that the process is not operable with a .DELTA..sup.1,4 -3-keto functionality in the steroid A-ring. Tet. Lett. 28, 1363 (1987) describes the peracid oxidation of a non-steroidal enol ether to give the corresponding epoxy-silyl ether and the subsequent isolation of a non-steroidal epoxy-silyl ether. In order to isolate the epoxy-silyl ether very mild reaction conditions were used and sodium bicarbonate was added to the reaction mixture to neutralize the acid product of the peracid reactant. Tet. Lett., 26, 3227 (1985) reports a steroidal epoxy-silyl ether where the epoxy-silyl ether functionality was in the steroid A-ring. This compound was not isolatable. The present invention does not require addition of a base such as sodium bicarbonate in order to isolate the 17.alpha.,20.alpha.-epoxy-20-silyl ether (IV).